Background: Array‐based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years’ postnatal clinical CMA application.Methods: DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide‐based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories.Results: A total of 140 non‐benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the “dysmorphism plus” category had the highest diagnostic yield.Conclusion: In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.

Secondary peritonitis (SP) remains a major clinical challenge due to its high complication rates and it often results in sepsis and multi-organ dysfunction. This study investigated the association between four nitric oxide synthase (NOS) single-nucleotide polymorphisms (SNPs)—NOS3 c.-786T>C (rs2070744), NOS3 c.894G>T (rs1799983), NOS3 27 bp variable number tandem repeat (VNTR) (rs61722009), and NOS2 (rs2297518)—and sepsis-related complications in 202 patients with SP. Demographic and baseline clinical characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Mannheim Peritonitis Index, and complications (multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and sepsis) were analyzed for associations with the NOS gene variants. Haplotype analysis was also performed. No SNP showed an association with in-hospital mortality. However, the NOS3 c.-786T>C TT genotype was significantly associated with an increased risk of MOF (p = 0.008), and remained independently associated after multivariate adjustment (p_MOF = 0.006). The T4bG haplotype was significantly more frequent among patients with MODS (p = 0.026), MOF (p = 0.048), and sepsis (p = 0.018). These findings suggest that NOS gene variants, particularly NOS3 c.-786T>C and the T4bG haplotype, may potentially serve as biomarkers for risk stratification in critically ill patients.

Congenital heart defects (CHDs) are the most common congenital anomalies, with identifiable genetic etiologies in approximately 5–30% of affected infants, depending on the clinical presentation and comorbidities. This study included 216 children with CHD, predominantly syndromic, to explore the role of genetic variants in their morphological phenotypes. Chromosomal microarray (CMA) and whole-exome sequencing (WES) were performed, revealing clinically significant copy number variations (csCNVs) in 27.3% of patients, with the most common deletions at 22q11.21 (11.9%) and 7q11.23 (8.5%). WES was conducted in 28.0% of cases, achieving a detection rate of 29.5%, primarily identifying variants related to Noonan syndrome. Genetic diagnoses were confirmed in 33.3% of patients, with clinically significant CNVs and SNV/INDELs found exclusively in those with syndromic CHD, leading to a 36.5% diagnosis rate in those patients. The identified variants most frequently affected genes encoding transcription factors (40.4%), followed by genes involved in the RAS signaling pathway and structural proteins (17.0%), and chromatin remodeling proteins (12.8%).

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE) is a common neurological outcome of perinatal asphyxia, with cerebral palsy (CP) being the most severe lasting effect. Perinatal brain injury activates the immune system and induces the release of inflammatory mediators. Matrix Metalloproteinases (MMPs) play a crucial role in neuroinflammation and neurodegeneration. This study explored the potential link between MMP2 promoter polymorphisms and the development of CP in children with a history of perinatal asphyxia. Methods: We enrolled 212 patients (130 males and 82 females) with documented perinatal asphyxia, who underwent a comprehensive neurological assessment and neuroimaging, including ultrasound and magnetic resonance imaging (MRI). We genotyped the MMP2 promoter polymorphisms rs243866, rs243865, and rs243864 using real-time polymerase chain reaction. Haplotype frequencies were calculated using Haploview software. Results: As expected, patients with HIE are more likely to develop CP (p = 0.000). In a study of 104 patients who developed CP, the frequencies of the A (rs243866), T (rs243865), and G alleles (rs243864) were nearly twice as high compared to those without CP (p = 0.008, p = 0.019, and p = 0.008, respectively). Haplotype analysis supported these findings, showing that the ATG haplotype was significantly more common among patients who developed CP (p = 0.004). Additionally, in patients with MRI-confirmed brain damage, the ATG haplotype was more frequently observed (p = 0.019). Conclusions: The ATG haplotype of the MMP2 promoter may indicate a risk factor for developing cerebral palsy (CP) in patients who experience perinatal asphyxia and could serve as a potential diagnostic predictor of CP.

Congenital heart defects (CHDs) are the most common congenital anomalies, with identifiable genetic etiologies in approximately 5–30% of affected infants, depending on the clinical presentation and comorbidities. This study included 216 children with CHD, predominantly syndromic, to explore the role of genetic variants in their morphological phenotypes. Chromosomal microarray (CMA) and whole-exome sequencing (WES) were performed, revealing clinically significant copy number variations (csCNVs) in 59 (27.3%) patients. The most frequent were 22q11.21 (8/59; 13.6%) and 7q11.23 (5/59; 8.5%) deletions. WES was conducted in 28.0% of cases, achieving a detection rate of 29.5%, primarily identifying variants related to Noonan syndrome. Genetic diagnoses were confirmed in 33.3% of patients, with clinically significant CNVs and SNV/INDELs found exclusively in those with syndromic CHD, leading to a 36.5% diagnosis rate in those patients. The identified variants most frequently affected genes encoding transcription factors (40.4%), followed by genes involved in the RAS signaling pathway and structural proteins (17.0%), and chromatin remodeling proteins (12.8%).

Objectives: Thrombolytic therapy with Alteplase is the standard treatment for eligible patients with acute ischemic stroke, but clinical response and hemorrhagic complications vary considerably among patients. This study aimed to investigate whether selected polymorphisms within the MMP-8 and MMP-9 genes are associated with baseline stroke severity, functional recovery, and hemorrhagic complications after thrombolytic therapy. Materials and Methods: Over a 24-month period, 166 Caucasian patients with acute ischemic stroke treated with intravenous Alteplase were prospectively enrolled. Genotyping was performed for MMP-9 rs3918241 and rs3918249, and MMP-8 rs1940475 and rs11225395 polymorphisms. Associations with neurological severity, functional outcome, and postthrombolytic hemorrhagic complications were analyzed. Haplotype analysis was performed for the investigated MMP-8 and MMP-9 variants. Results: No significant associations were observed between the investigated MMP-9 polymorphisms and functional recovery or hemorrhagic complications after Alteplase treatment. However, carriers of the MMP-9 rs3918249 T allele had lower National Institutes of Health Stroke Scale scores at admission, suggesting a less severe initial clinical presentation. For MMP-8 , patients who developed symptomatic intracerebral hemorrhage were significantly more likely to carry the rs1940475 TT genotype ( P = 0.032; odds ratio = 5.10; 95% CI: 1.27-20.56). Haplotype analysis showed strong linkage disequilibrium between rs1940475 and rs11225395, and the TG haplotype was significantly more frequent in patients without hemorrhagic transformation than in those with hemorrhagic transformation. Conclusions: The investigated MMP-9 polymorphisms were not associated with postthrombolytic recovery or hemorrhagic complications. In contrast, MMP-8 rs1940475 and MMP-8 haplotypes may be related to hemorrhagic risk after Alteplase therapy.